Structure of DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA

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Structure of DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA. / He, Yangzi; Staley, Jonathan P; Andersen, Gregers Rom; Nielsen, Klaus H.

In: RNA, Vol. 23, 2017, p. 1110-1124.

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He, Yangzi ; Staley, Jonathan P ; Andersen, Gregers Rom ; Nielsen, Klaus H. / Structure of DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA. In: RNA. 2017 ; Vol. 23. pp. 1110-1124.

Bibtex

@article{f6fd08e35b9847288633ee260b3d8025,
title = "Structure of DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA",
abstract = "Three families of nucleic acid-dependent ATPases (DEAH/RHA, Ski2-like and NS3/NPH-II), termed the DExH ATPases, are thought to execute myriad functions by processive, ATP-dependent, 3' to 5' translocation along single-stranded nucleic acid. While the mechanism of translocation of the viral NS3/NPH-II family has been studied extensively, it has not been clear if or how the principles that have emerged for this family extend to the other two families. Here we report the crystal structure of the yeast DEAH/RHA family ATPase Prp43p, which functions in splicing and ribosome biogenesis, in complex with poly-uracil and a non-hydrolysable ATP analogue. The structure reveals a conserved DEAH/RHA-specific variation of motif Ib within the RecA1 domain of the catalytic core, in which the motif elongate as a β-hairpin that bookends the 3' end of a central RNA stack, a function that in the viral and Ski-2 families is performed by an auxiliary domain. Supporting a fundamental role in translocation, mutations in this hairpin abolished helicase activity without affecting RNA binding or ATPase activity. While the structure reveals differences with viral ATPases in the RecA1 domain, our structure demonstrates striking similarities with viral ATPases in the RecA2 domain of the catalytic core, including both a prominent β-hairpin that bookends the 5' end of the RNA stack and a dynamic motif Va that is implicated in mediating translocation. Our crystal structure, genetic and biochemical experiments, as well as comparisons with other DExH ATPases support a generalized mechanism for the DExH class of helicases involving a pair of bookends that inchworm along RNA.",
keywords = "Journal Article",
author = "Yangzi He and Staley, {Jonathan P} and Andersen, {Gregers Rom} and Nielsen, {Klaus H}",
note = "Published by Cold Spring Harbor Laboratory Press for the RNA Society.",
year = "2017",
doi = "10.1261/rna.060954.117",
language = "English",
volume = "23",
pages = "1110--1124",
journal = "RNA",
issn = "1355-8382",
publisher = "Cold Spring Harbor Laboratory Press",

}

RIS

TY - JOUR

T1 - Structure of DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA

AU - He, Yangzi

AU - Staley, Jonathan P

AU - Andersen, Gregers Rom

AU - Nielsen, Klaus H

N1 - Published by Cold Spring Harbor Laboratory Press for the RNA Society.

PY - 2017

Y1 - 2017

N2 - Three families of nucleic acid-dependent ATPases (DEAH/RHA, Ski2-like and NS3/NPH-II), termed the DExH ATPases, are thought to execute myriad functions by processive, ATP-dependent, 3' to 5' translocation along single-stranded nucleic acid. While the mechanism of translocation of the viral NS3/NPH-II family has been studied extensively, it has not been clear if or how the principles that have emerged for this family extend to the other two families. Here we report the crystal structure of the yeast DEAH/RHA family ATPase Prp43p, which functions in splicing and ribosome biogenesis, in complex with poly-uracil and a non-hydrolysable ATP analogue. The structure reveals a conserved DEAH/RHA-specific variation of motif Ib within the RecA1 domain of the catalytic core, in which the motif elongate as a β-hairpin that bookends the 3' end of a central RNA stack, a function that in the viral and Ski-2 families is performed by an auxiliary domain. Supporting a fundamental role in translocation, mutations in this hairpin abolished helicase activity without affecting RNA binding or ATPase activity. While the structure reveals differences with viral ATPases in the RecA1 domain, our structure demonstrates striking similarities with viral ATPases in the RecA2 domain of the catalytic core, including both a prominent β-hairpin that bookends the 5' end of the RNA stack and a dynamic motif Va that is implicated in mediating translocation. Our crystal structure, genetic and biochemical experiments, as well as comparisons with other DExH ATPases support a generalized mechanism for the DExH class of helicases involving a pair of bookends that inchworm along RNA.

AB - Three families of nucleic acid-dependent ATPases (DEAH/RHA, Ski2-like and NS3/NPH-II), termed the DExH ATPases, are thought to execute myriad functions by processive, ATP-dependent, 3' to 5' translocation along single-stranded nucleic acid. While the mechanism of translocation of the viral NS3/NPH-II family has been studied extensively, it has not been clear if or how the principles that have emerged for this family extend to the other two families. Here we report the crystal structure of the yeast DEAH/RHA family ATPase Prp43p, which functions in splicing and ribosome biogenesis, in complex with poly-uracil and a non-hydrolysable ATP analogue. The structure reveals a conserved DEAH/RHA-specific variation of motif Ib within the RecA1 domain of the catalytic core, in which the motif elongate as a β-hairpin that bookends the 3' end of a central RNA stack, a function that in the viral and Ski-2 families is performed by an auxiliary domain. Supporting a fundamental role in translocation, mutations in this hairpin abolished helicase activity without affecting RNA binding or ATPase activity. While the structure reveals differences with viral ATPases in the RecA1 domain, our structure demonstrates striking similarities with viral ATPases in the RecA2 domain of the catalytic core, including both a prominent β-hairpin that bookends the 5' end of the RNA stack and a dynamic motif Va that is implicated in mediating translocation. Our crystal structure, genetic and biochemical experiments, as well as comparisons with other DExH ATPases support a generalized mechanism for the DExH class of helicases involving a pair of bookends that inchworm along RNA.

KW - Journal Article

U2 - 10.1261/rna.060954.117

DO - 10.1261/rna.060954.117

M3 - Journal article

C2 - 28416566

VL - 23

SP - 1110

EP - 1124

JO - RNA

JF - RNA

SN - 1355-8382

ER -